Natural products and nature-derived materials continue to represent major analytical challenges in biomedical research. Their innate chemical complexity is of biogenetic origin, and can obscure correlations between chemical structures and observed biological effects. Thus, analytical methodology becomes most important in the identification of active principles and the definition of reference standards. This concise summary fully characterizes the current situation of botanical dietary supplements (botanicals), which represent natural health products that are widely sold to and consumed by the U.S. public. According to the 2008 National Health Statistics Report, almost one in ten persons (30 mio.) use botanicals and belong to the 40% of the population who use complementary and alternative medicine (CAM). Novel analytical technologies that can comprehensively assess the integrity of botanical preparations and related natural products are in high demand and can potentially accelerate progress in basic and clinical sciences. The broad goal of this project is to advance the current analytical methodology for natural products to a new level and implement a new state-of-the-art in the assessment of the integrity of botanical materials and reference standards. The development of cutting-edge methods in nuclear magnetic resonance (NMR) and hyphenated mass spectroscopy (MS) will provide an innovative approach to the complexity of botanicals and transform the current state-of-the-art in the characterization of natural health products. In order to achieve this goal, the project will capitalize on the unique combination of investigator expertise (pioneers in quantitative NMR [qNMR], mass spectrometry skills), infrastructure (first-class NMR facility), and interdisciplinary research environment (UIC pharmacognosy group) to address the fundamental research problem of chemical complexity of herbal preparations. The project will develop innovative spectrometric technologies (qNMR, UHPLCQTRAP- MS) for broad implementation into dietary supplement research and production workflows. Groundbreaking research in this direction is especially timely in light of abundant concerns about the efficacy and safety botanicals as advocated by NCCAM/ODS/NIH, and the safety of "functional foods" as advocated by FDA. The new methodology will be initially established for 10 of the top-20 most widely used botanicals. The immediate outcome is new spectrometric platform technology for the verification of origin, identity, and clinical integrity of botanical products. Assurance of product integrity parameters is at the core of NIH/NCCAM/ODS'mission to explore CAM in the context of rigorous science. Going beyond natural product integrity, project outcome will provide new leverage on the inherent complexity of natural products, and foster interdisciplinary biomedical research aimed at the rationalization of the botanicals used for human health. Public Health Relevance: This project seeks to establish new spectrometric technologies for the assessment of the quality and integrity of botanical dietary supplements, which are widely consumed by the U.S. public and a major health economy factor. The development of integrated cutting-edge methodology using magnetic resonance (MR) and mass spectrometry (MS) will provide an innovative approach to botanical reference standards and can transform the current state-of-the-art in the characterization of natural health products. The project will build a unique resource to be maintained within the highly interdisciplinary pharmacognosy research environment at the University of Illinois at Chicago (UIC) and to be made broadly available for translational clinical research involving botanicals and other natural products.